Its report, Research Involving Children, ultimately became the foundation for pediatric research regulations adopted in 1983. These regulations, which were codified in Subpart D of 45 CFR Part 46, are at the heart of the Presidential Commission for the Study of Bioethical Issues’ discussions of pediatric medical countermeasures research at Meeting 12 held in Miami, Florida.

Most provisions of 45 CFR Part 46 provide general protections for human subjects research with adults. In formulating the principles that animate Subpart D, the National Commission maintained the view that children, as a separate class, must be given additional protections in the context of research; unlike adults, children cannot provide informed consent to research and therefore constitute a “vulnerable” population. The National Commission developed standards for pediatric research protections intended to both adequately protect children and allow beneficial or important pediatric research to take place.

The regulations of Subpart D provide four ways to determine whether pediatric research is permissible based on the National Commission’s recommendations in Research Involving Children. The first, described under 45 CFR § 46.404 (referred to as Section 404), permits research with children that presents no greater than minimal risk, or risk equivalent to that which children encounter in their daily lives, as long as adequate measures are taken to solicit informed parental permission and meaningful child assent, and other research protections, such as independent review, are in place.

The second category, Section 405, provides standards for research that presents greater than minimal risk, but is justified by the expected direct benefit to research participants – a benefit at least as favorable as alternative interventions.

Section 406 permits IRBs to approve research that is greater than minimal risk and does not offer direct benefit to participants if the research is likely to yield knowledge about participants’ condition and meets other ethical and regulatory requirements.

Finally, Section 407 regulates research that cannot be approved under 404, 405, or 406, but presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children. Unlike research approved under sections 404, 405, and 406, research reviewed under this provision cannot be approved by a local institutional review board; rather it must be assessed by a national review panel and can only be approved by the Secretary of Health and Human Services. This type of review is rare.

Each type of review in Subpart D requires researchers to obtain both parental permission, and child assent, where meaningful before children can participate.

A major part of the current Commission’s deliberations today and tomorrow concerns how to best apply the ethical foundations underlying the regulations in Subpart D to pediatric medical countermeasure research in general and to anthrax vaccine research in particular.

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